Many medical procedures in use today require a relatively small sample of blood (e.g., 5-50 micro-liters) This blood is often obtained by lancing or piercing the skin (e.g., of the finger) with a needle of a spring-loaded lancet to enable the collection of 1 or 2 drops of blood. See, e.g., U.S. Pat. Nos. 4,503,856 and 4,517,978. This lancing procedure, however, can be quite painful due to the highly sensitive skin at the fingers. Furthermore, to facilitate the blood collection, some forms of pressure gradients, such as either applying a positive pressure (e.g., by squeezing) or a negative pressure (i.e., a suction), is often required to be applied to the cut. See, e.g., U.S. Pat. Nos. 4,637,403, 4,654,513, 5,320,607, and 5,368,047.
Unfortunately, diabetic patients have to endure this painful lancing procedures several times a day, in addition to insulin injections, in order to have a tight control of their blood glucose levels, as the treatment requires. Repeated lancing in limited surface areas (such as on the fingertip) may result in the formation of calluses. This leads to increased difficulty in drawing blood and increased pain. Moreover, the need to obtain a small blood sample for other home use diagnostic applications (e.g., for cholesterol monitoring) is becoming more commonplace. It, therefore, is desirable to develop a blood sampling method that eliminates the use of needles/lancets and is free of pain or discomfort. It is also desirable to be able to obtain biological fluid samples from other skin sites that are less sensitive than fingers.
For both drug delivery and biological fluid sampling, non-invasive and minimally invasive methods are preferred over invasive methods (e.g., needle injection) since they may easily be self-administered and are pain free. U.S. Pat. Nos. 5,250,028 and 5,843,113, PCT Patent Applications Nos. WO98/11937 and WO97/48440, and Henry et al (Microfabricated Microneedles: A Novel Approach to Transdermal Drug Delivery, S. Henry, D. V. McAllister, M. G. Allen and M. R. Prausnitz, Journal of Pharmaceutical Sciences, Vol. 8, August 1998, pages 922-925), disclose perforation or disruption of the skin barrier membrane with mechanical means, e.g., with either small blades or needles, for such purposes. U.S. Pat. Nos. 5,421,816; 5,445,611 and 5,458,140 disclose, as a replacement for invasive sampling, the use of ultrasound to act as a pump for expressing interstitial fluid directly through visually intact (i.e., non-lanced) skin. Other means of treating a tissue to increase transiently the tissue permeability to enhance molecular transport for drug delivery and/or for sampling of interstitial fluids are disclosed in U.S. Pat. Nos. 5,019,034, 5,547,467, 5,667,491, 5,749,847, 5,885,211, and 5,441,490 and PCT Patent Application WO 95/12357.
The object of the present invention is to provide a device and a method using a shear device to perforate the skin barrier for obtaining a sample of a bodily fluid through a membrane and/or deliver an active agent (e.g., for therapeutic purposes). The method disclosed in this invention is needle-less and painless, and is particularly suitable to obtain the biological fluid from less sensitive skin areas other than fingers.